INDUSTRIAL CHEMICAL TOXICOLOGY_2024.pdf

INDUSTRIAL CHEMICAL TOXICOLOGY  Introduction The organic solvent comprises a large & diverse group of industrially important chemical compounds. Despite advances in worker protection standards, such exposures remain a health concern to millions of worke...

INDUSTRIAL CHEMICAL TOXICOLOGY  Introduction The organic solvent comprises a large & diverse group of industrially important chemical compounds. Despite advances in worker protection standards, such exposures remain a health concern to millions of workers throughout the world Physicochemical Properties of Representative Solvents and Related Materials continued  Physicochemical Properties of Representative Solvents and Related Materials The Principles of Toxicology. Environmental and Industrial Applications. 2nd edition The breadth of structural variability and the range of physicochemical properties exhibited by organic solvents limits the number of generalized observations that can be made regarding physiological effects and exposure hazards. Occupational Exposure Guideline Definitions The Principles of Toxicology. Environmental and Industrial Applications. 2nd edition  ADME Characteristic of volatility ➔ solvent exposure occurs via the inhalation route (mainly). There also may be absorption through the skin following exposures to vapors or through direct contact with the liquid form. Absorption by lung: – Pulmonary ventilation rate – Depth of respiration – Pulmonary circulation rate Partition coefficients??? Metabolism ➔ biotransformation  Health Effects Depression of CNS. Peripheral nervous system – distal axonal peripheral neuropathy. Membrane & tissue irritation. Carcinogenecity Other - acute effects may include hepatotoxicity, nephrotoxicity, and cardiac arrhythmias. The Principles of Toxicology. Environmental and Industrial Applications. 2nd edition  TOXIC PROPERTIES OF REPRESENTATIVE ALIPHATIC ORGANIC SOLVENTS Saturated Aliphatic Solvents: CnH2n+2 (alkanes/parafin) – irritating to mucous membranes – anesthetic properties (relatively weak). – asphyxiant potential. – neurotoxic (e.g., n-hexane) – Symptoms of acute exposure nausea, vomiting, cough, pulmonary irritation, vertigo or dizziness, slow and shallow respiration, narcosis, coma, convulsions, and death – Chronic exposure hexane and heptane ➔ neuropathy – symptoms: muscle pain and spasms, muscular weakness, and paresthesias.  TOXIC PROPERTIES OF REPRESENTATIVE ALIPHATIC ORGANIC SOLVENTS Unsaturated Aliphatic Solvents: C n H 2n (alkenes/olefins) – Exhibit qualitative toxicological properties similar to those of the alkanes. – Unsaturated nature of the hexene and heptene series apparently largely abolishes the neurotoxic effects that have been reported following chronic hexane or heptane exposure ➔ why?? TOXIC PROPERTIES OF REPRESENTATIVE ALICYCLIC SOLVENTS Toxicological properties resemble those of their open-chain relatives. Exhibit anesthetic or CNS-depressant properties at high exposure concentrations.  TOXIC PROPERTIES OF REPRESENTATIVE AROMATIC HYDROCARBON SOLVENTS Typically cause more tissue irritation than the corresponding molecular weight aliphatics or alicyclics. (skin, eyes, pulmonary) Once absorbed and in systemic circulation, these hydrocarbons are demonstrably more toxic. CNS depression is a major acute effect. Benzene, substituted aromatic compounds (alkylbenzene- toulene, xylene; PAHs) Benzene – carcinogen; alkylbenzene ≠ carcinogen Toulene > benzene – CNS depressant effect. PAH such as benzo(a)pyrene – carcinogen.  TOXIC PROPERTIES OF REPRESENTATIVE ALCOHOLS Alcohol Compounds: R–OH – Alcohols are more powerful CNS depressants than their aliphatic analogues. – Irritants. – Methanol – unique toxicity to the eyes. Glycols – Ethylene glycol ➔metabolism to oxalate (or oxalic acid) obstructive renal failure (formation of oxalate crystals) Phenols – ability to denature and to precipitate proteins. – corrosive and severe burns may result from direct contact. – limited local anesthetic properties – CNS depressant  TOXIC PROPERTIES OF REPRESENTATIVE ALDEHYDES Primary irritation of the skin, eyes, and mucosa of the respiratory tract – (> in lower molecular weights & unsaturated aliphatic chains). Although can produce narcosis, this effect rarely is observed. WHY?? Sensitization – an endpoint common to aldehydes. Formaldehyde ≠ reproductive toxicities /teratogenicity. Formaldehyde = carcinogenic Formaldehyde  TOXIC PROPERTIES OF REPRESENTATIVE KETONES Ketones are recognized CNS depressants The vapors present at concentrations that are great enough to cause sedation also are strongly irritating to the eyes and respiratory passages. Acetone – drowsiness, skin and eyes irritation Acetone  TOXIC PROPERTIES OF REPRESENTATIVE ETHERS Ethers are effective anesthetics, and this property increases with the molecular size. Irritant. Easily oxidized or photodegraded to peroxides which may be quite explosive. As chain length increases for the ethers, the oral and inhalation toxic potential decreases. However, dermal penetrability and skin irritation increases with increasing chain length. Diethyl ether – produces anesthesia and slightly irritating to the skin and eyes. – induces respiratory arrest.  TOXIC PROPERTIES OF REPRESENTATIVE HALOGENATED SOLVENTS Halogenated compounds exhibit strong dermal irritant effects. I>Br>Cl>F ➔ toxicity. A drawback to the widespread use of halogenated alkanes is that some of these compounds (e.g., 1,2-dichloroethane). Chronic exposure to certain haloalkanes has been implicated in human cases of degenerative cardiac disease. Methyl chloride – considered a weak to moderate irritant (eyes & skin). – intoxication state similar to drunkenness or inebriation – Chronic and subacute exposure predominantly affects the CNS. – Cardiac degeneration and depression of bone marrow  TOXIC PROPERTIES OF REPRESENTATIVE HALOGENATED SOLVENTS Chloroform teratogenic and highly embryotoxic. does not induce chromosome breakage or sister– chromatid exchanges in human lymphocytes and produce mutagenic changes in cultures of Chinese hamster lung fibroblast cells. Carbon tetrachloride The odor is one to which individuals often becomes adapted, and odor is not a satisfactory warning of excessive exposure. is not significantly teratogenic. CNS depression Liver and kidney injury.  TOXIC PROPERTIES OF REPRESENTATIVE HALOGENATED SOLVENTS Vinyl chloride A gas under ambient conditions. A potent skin irritant. Contact with the liquid form may cause frostbite. Depresses the central nervous system, causing sy m pto m s that re s e m b l e mild a lcohol intoxication. Chronic exposure may damage the liver and i n d u c e a h i g h l y s p e c i f i c l i v e r c a n c e r (angiosarcoma)  Determinants of a solvent’s inherent toxicity Number of carbon atoms. Whether it is saturated or has double/triple bonds between adjacent carbon atoms. Its configuration. Presence of functional group.  THANK YOU Email: [email protected] The Principles of Toxicology. Environmental and Industrial Applications. 2nd edition (Philip L. Williams, Robert C. James & Stephen M. Roberts) Casarett and Doull’s Toxicology. The Basic Science of Poisons 8th edition (Curtis D. Klaassen)